Expression of alpha2- and beta2-adrenergic responses by hepatocyte growth factor and platelet-derived growth factor in primary cultures of adult rat hepatocytes.
We investigated the effects of hepatocyte growth factor (HGF) and platelet-derived growth factor (PDGF) on the expression of alpha2- and beta2-adrenergic responses in primary cultures of adult rat hepatocytes. HGF (1 and 5 ng/ml) rapidly stimulated the expression of beta2-adrenergic responses and significantly increased alpha2-adrenergic responses with a maximal response at 21 h. The stimulatory effects of HGF were reduced dependent on the initial plating density and were completely blocked by cycloheximide (5 microM). On the other hand, PDGF (10 ng/ml) significantly increased the beta2-adrenergic response, but only slightly increased the alpha2-adrenergic responses. Expression of the alpha2- and beta2-adrenergic responses by PDGF was independent of the initial plating density. The expression of these responses was blocked by cycloheximide (5 microM). Northern blot analysis of the hepatocyte mRNA showed increased expression induced by the HGF and PDGF of the both alpha2- and beta2-adrenergic receptor mRNA, and this expression was inhibited by actinomycin D (5 ng/ml). These results indicate that the expression of alpha2- and beta2-adrenergic responses produced by these two growth factors is regulated differently by the cell density of the primary cultures. The results suggest that the expression of alpha2- and beta2-adrenergic responses is mediated through increased synthesis of these receptor proteins.
Kimura
M
M
Biochemical Pharmacology Group, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
Ogihara
M
M
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015152:Blotting, Northern; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D003513:Cycloheximide / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000096:biosynthesis; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis; D013498:Suramin / Q000494:pharmacology
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000970:Antineoplastic Agents; D010982:Platelet-Derived Growth Factor; D011500:Protein Synthesis Inhibitors; D018341:Receptors, Adrenergic, alpha-2; D018343:Receptors, Adrenergic, beta-2; D013498:Suramin; D017228:Hepatocyte Growth Factor; D003513:Cycloheximide; D000242:Cyclic AMP